VPS26A

VPS26A

Target · Retromer subunit

VPS26A VPS26 retromer complex component A · Vacuolar protein sorting-associated protein 26A

VPS26A (VPS26 retromer complex component A, also known as Hbeta58, PEP8A or VPS26) is a component of the retromer cargo-selective complex. It helps prevent selected transmembrane cargo proteins from being missorted into the lysosomal degradation pathway. Browse Assay Genie's current range of VPS26A research reagents below, or read on for the biology behind the target.

Endosome membrane proteinRetromer cargo-selective complexInteracts directly with VPS35
327 aa
Protein length
~38 kDa
Molecular weight
10q22.1
Gene locus
VPS26 family
Protein family
Target information

What is VPS26A (VPS26 retromer complex component A)?

VPS26A acts as a component of the retromer cargo-selective complex (CSC), which is believed to be the core functional unit of retromer and its complex variants. The CSC prevents selected transmembrane cargo proteins from being missorted into the lysosomal degradation pathway. Recruitment of the CSC to the endosomal membrane involves RAB7A and SNX3. The CSC also appears to act as a recruitment hub for other proteins, including the WASH complex and TBC1D5, and VPS26A is required for the endosomal localisation of both WASHC2A and TBC1D5.

Within different retromer assemblies, VPS26A contributes to several trafficking routes. The SNX-BAR retromer mediates retrograde transport of cargo from endosomes to the trans-Golgi network (TGN) and endosome-to-plasma membrane recycling. The SNX3-retromer carries WLS from endosomes to the TGN by a route distinct from the SNX-BAR pathway. The SNX27-retromer is believed to support endosome-to-plasma membrane recycling of a broad range of cargo, and VPS26A enhances the affinity of SNX27 for PDZ-binding motifs in cargo proteins. It is required for retrograde transport of the lysosomal enzyme receptor IGF2R and for transcytosis of the polymeric immunoglobulin receptor. It also mediates retromer recognition of SORL1, which is implicated in sorting and processing of APP, is involved in recycling of ADRB2, and acts in retromer-independent lysosomal sorting of F2R.

The VPS26A gene belongs to the vacuolar protein sorting (VPS) gene group, and the protein belongs to the VPS26 family. It is found in the cytoplasm and on early endosome membranes. Expression studies in yeast and mammalian cells indicate that it interacts directly with VPS35, which serves as the core of the retromer complex. The close structural similarity between yeast and human retromer proteins suggests conserved function, and alternative splicing gives multiple transcript variants encoding different isoforms. Orthologues are named Vps26a in mouse and rat. Earlier names include vacuolar protein sorting 26 (yeast homolog).

Endosomal cargo sorting

VPS26A is part of the retromer cargo-selective complex that keeps selected transmembrane proteins out of the lysosomal degradation pathway.

Retrograde transport to the TGN

Retromer assemblies containing VPS26A mediate endosome-to-TGN transport, including SNX3-dependent transport of WLS and IGF2R retrieval.

Receptor recycling and transcytosis

VPS26A is involved in plasma membrane recycling of cargo such as ADRB2 and in transcytosis of the polymeric immunoglobulin receptor.

SORL1 and APP processing

VPS26A mediates retromer recognition of SORL1, which is implicated in the sorting and processing of APP.

Background

VPS26A frequently asked questions

What does VPS26A do?

VPS26A is a subunit of the retromer cargo-selective complex. It helps retrieve selected transmembrane cargo from endosomes for transport to the trans-Golgi network or the plasma membrane, so that the cargo avoids lysosomal degradation. It also helps recruit the WASH complex and TBC1D5 to endosomes.

What other names does VPS26A go by?

VPS26A is also called Hbeta58, PEP8A and VPS26. Earlier names include vacuolar protein sorting 26 (yeast homolog) and vacuolar protein sorting 26 homolog A (S. pombe). Alternative splicing produces multiple transcript variants that encode different isoforms.

Is VPS26A conserved across species?

Yes. The close structural similarity between yeast and human retromer proteins suggests a similar function. Mouse and rat both have a Vps26a orthologue. Check the datasheet of any product for its validated reactivity.

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Related targets

VPS35, the direct retromer partner of VPS26A, and other vacuolar protein sorting family members involved in endosomal trafficking.

Gene and protein annotations from HGNC, NCBI Gene and UniProt O75436; product specifications from Assay Genie datasheets.

VPS26A Product listing